DESCRIPTION (provided by investigator): The lack of scientific attention devoted to the placebo effect as a phenomenon in its own right probably reflects the paucity of theoretical positions within which to organize the existing data and design new research. This research proposal addresses the clinical significance of behavior-sympathetic system interactions, and will advance the analysis of the placebo effect from a descriptive to an experimental analysis as a reflection of learning processes. Conditioning is an inherent component of most pharmacotherapeutic regimens. The proposed research will capitalize on conditioned responses to reduce the cumulative amount of carvedilol used in the treatment of hypertension. Patients would continue to be treated with carvedilol, but experimental patients would be shifted from their current schedule of continuous reinforcement (active drug whenever medication is taken) to a partial schedule of reinforcement (active drug a percentage of the time and placebo at other times). To equate amounts of medication, other patients would be treated with a reduced dose of carvedilol in a standard treatment regimen. It is hypothesized that, holding the cumulative dose constant, a partial schedule of reinforcement will enable patients to maintain a lower cumulative amount of carvedilol than patients treated under a continuous schedule of active drug. Hypertension is an especially appropriate model to evaluate the therapeutic effect of partial schedules of pharmacologic reinforcement, which could decrease the amount of total drug required and the deleterious side effects of long-term carvedilol treatment. It may be possible to increase the benefit:/risk ratio of drug therapy and reduce the costs of medication. The proposed research is not an attempt to offer a behavioral alternative to drug treatment; it is an attempt to add a behavioral dimension to the design of drug treatment protocols allowing for the reduction in the dosage of anti-hypertensive medication. This is an attempt to adopt conditioning principles and use schedules of reinforcement to design regimens of systemic drug therapy. If proven effective, this new approach to pharmaco- therapy and placebo effects is likely to stimulate new interdisciplinary research in neuro- pharmacology. PUBLIC HEALTH RELEVANCE: This study will determine if principles of Pavlovian classical conditioning can be applied to the treatment of patients with hypertension. We will treat patients with mild hypertension with carvedilol, and once they have learned the hypotensive effects of the drug, the total amount of drug will be reduced by providing a full dose of drug on only one of every four treatment occasions and an identical placebo on three of every four treatment occasions. If we succeed in proving that patients can be treated with less drug by adding placebos to their regimen, it will have a very significant impact on the manner in which patients suffering from chronic diseases are treated in the future, since it may be applied to a wide variety of medical conditions. This will decrease the overall cost as well as reducing the deleterious side-effects of drugs.